Crafting Stable Antibiotic Nanoparticles via Complex Coacervation of Colistin with Block Copolymers.

To combat the ever-growing increase of multidrug-resistant (MDR) bacteria, action must be taken in the development of antibiotic formulations. Colistin, an effective antibiotic, was found to be nephrotoxic and neurotoxic, consequently leading to a ban on its use in the 1980s. A decade later, colistin use was revived and nowadays used as a last-resort treatment against Gram-negative bacterial infections, although highly regulated. If cytotoxicity issues can be resolved, colistin could be an effective option to combat MDR bacteria. Herein, we investigate the complexation of colistin with poly(ethylene oxide)-b-poly(methacrylic acid) (PEO-b-PMAA) block copolymers to form complex coacervate core micelles (C3Ms) to ultimately improve colistin use in therapeutics while maintaining its effectiveness. We show that well-defined and stable micelles can be formed in which the cationic colistin and anionic PMAA form the core while PEO forms a protecting shell. The resulting C3Ms are in a kinetically arrested and stable state, yet they can be made reproducibly using an appropriate experimental protocol. By characterization through dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS), we found that the best C3M formulation, based on long-term stability and complexation efficiency, is at charge-matching conditions. This nanoparticle formulation was compared to noncomplexed colistin on its antimicrobial properties, enzymatic degradation, serum protein binding, and cytotoxicity. The studies indicate that the antimicrobial properties and cytotoxicity of the colistin-C3Ms were maintained while protein binding was limited, and enzymatic degradation decreased after complexation. Since colistin-C3Ms were found to have an equal effectivity but with increased cargo protection, such nanoparticles are promising components for the antibiotic formulation toolbox.

General joint hypermobility in temporomandibular joint disease; clinical characteristics, biomarkers, and surgical aspects.

Objectives: This study aimed at identifying biomarkers in the temporomandibular joint (TMJ) synovial tissue analysing 28 extra cellular matrix proteins in TMJ diseased patients, classified with either general joint hypermobility (GJH) or normal joint mobility (NJM), and to compile clinical and protein characterisation to reveal potential surgical predictive factors. Study design: A prospective observational cohort study including 97 consecutive patients scheduled for TMJ surgery was performed. Joint mobility and several other predefined clinical variables were recorded. Synovial tissue was harvested during surgery followed by examination using multi-analytic profiling. A multivariate quantile regression model was used for analysis purposes. Results: The GJH/NJM ratio was 2:5. The GJH cohort were younger (P = 0.001) and more likely to be women (P = 0.026) compared to the NJM cohort. None of the protein concentrations could be correlated to joint mobility in the multivariate regression model, but often to the variable TMJ diagnosis. The surgical outcome after the six-month follow-up were equal between GJH and NJM patients. Conclusions: GJH was more common in the study cohort compared to general population frequencies, but GJH was not a negative factor for surgical outcome. Young age and female gender correlated to GJH. No TMJ biomarkers were GJH specific, and the results suggested that TMJ diagnosis more strongly correlated to the protein profile compared to GJH and the other investigated variables.